Cancer refers to a group of diseases wherein a mass or tumor of undifferentiated cells that grow unregulatedly and unlimitedly is formed in tissues. By infiltrating into and destroying nearby normal tissues or organs and metastasizing from the primary site a new site in other tissues or organs, it can ultimately take the life of an organism.
For decades, a lot of nanomaterials and drugs have been attempted as contrast agents targeting cancer cells or targeted drug delivery systems. Among them, the ‘active targeting system’ based on the genetic information of cancer cells has provided an insight for remarkable cancer cell targeting efficiency. However, the currently achievable cancer cell targeting efficiency is still limited and there are many obstacles in improving the targeting efficiency. In particular, the current active targeting strategy based on genetic information has intrinsic limitations because the receptors present on the cancer cell surface are restricted in their type or amount. In addition, the heterogeneity of cancer cells makes the situation even more complicated due to various mutations of the cancer cells that express receptors of different types and amounts. This heterogeneity is observed even within the tumor cells of the same tissue. As a result, many nanomaterials and drugs targeting the receptors present on the cancer cell surface can be easily saturated with the receptors and this leads to decreased efficiency of targeted imaging or targeted drug delivery.
Therefore, if targetable chemical groups can be introduced into cancer tissues containing heterogeneous cancer cells, they can be used as artificial active targeting sites for delivery of nanomaterials. This is expected to be a solution for overcoming the heterogeneity of cancer cells.
Recently, Bertozzi et al. developed a metabolite cleaved by the prostate-specific antigen protease and demonstrated the introduction of azide groups into cancer cells in vitro. However, they did not present an in-vivo experiment result (non-patent document 1).
Cathepsin B is one of cysteine proteases. Increased amount of its mRNA as compared to normal cells is reported in human-derived prostate cancer cells (non-patent document 2), colorectal cancer cells (non-patent document 3), glioma cells (non-patent document 4) and melanoma cells (non-patent document 5). Also, increased expression and activity of the enzyme is reported in breast cancer, colon cancer, esophageal cancer, stomach cancer, lung cancer, uterine cancer and thyroid cancer (non-patent document 6). In particular, increased expression of cathepsin B is reported in metastatic cancer (non-patent documents 7 and 8).